1. Field of the Invention
The invention relates optically active cis-1,3-cyclohexanedicarboxylic acid monoesters of high enantiomeric purity. The invention also relates a method of preparing optically active cis-1,3-cyclohexanedicarboxylic acid monoesters of high enantiomeric purity. The monoesters may be used as chiral precursors for non-naturally occuring amino acids such as those used to prepare a variety of pharmaceuticals. The monoesters or their derivatives may also be used as chiral polyester modifiers to change the plasticity, melting point, glass transition temperature, chirality or other properties of the polyester.
2. Description of the Related Art
Enzyme-catalyzed hydrolysis reactions are known methods for the generation of asymmetry within a molecule. Oftentimes racemic mixtures of a compound are subjected to enzyme-catalyzed hydrolysis to aid in the resolution of the racemic mixture, i.e. the separation of a racemic mixture into its two optically active components. However, such reactions are often inefficient and at best afford a 50% yield of each enantiomer. In an effort to improve efficiency, enzyme-catalyzed hydrolysis of prochiral meso substrates rather than racemic mixtures has been attempted.
Enantioselective enzyme-catalyzed hydrolysis of cis-1,2-isomers of cyclohexane-dicarboxylic acid diesters has been achieved using the enzyme pig liver esterase. Jones et al., J. Org. Chem. 52, 4565 (1987); Gais et al., Leibings Ann. Chem. 687 (1986); Lam et al., J. Am. Chem. Soc. 110, 4409 (1988); Schneider et al., Angew. Chem. Int. Ed. Engl. 23, 67 (1984). The 1,2-isomers have found use in the synthesis of both pharmaceutically active materials and natural products. Turbanti et al., J. Med. Chem. 36, 699 (1993); EP 337,348; Hamilton et al., J. Org. Chem. 58, 7263 (1993); WO 92 10,099; Brion et al., J. Tetrahedron Lett. 34, 4889 (1994); Borzilleri et al., J. Am. Chem. Soc. 116, 9789 (1994).
There have also been reports of the desymmetrization of both cis-1,3-cyclopentane-dicarboxylic anhydride via enzymatic alcoholysis and cis-1,3-cyclopentanedicarboxylic acid diesters via enzyme-catalyzed hydrolysis. Chenevert et al., Tetrahedron; Asymmetry. 3, 199 (1992); Chenevert et al., Chem. Lett. 93 (1994). However, only a single sense of asymmetry, i.e. one enantiomer, was realized in each case. Furthermore, the one enantiomer could only be obtained in .ltoreq.91% ee.
In theory, such selective reactions of one of the prochiral groups of the meso substrate would lead to the "desymmetrization" of the meso substrate and theoretically may optimally afford a 100% yield of an optically pure product. This type of process has been termed the "meso trick." Enzyme-catalyzed hydrolysis of a "meso" substrate would also offer the advantage of producing a single species where the reaction of a racemate produced two--an ester of one enantiomer and an alcohol or acid of the other. Thus, an additional separation step is avoided by application of a desymmetrization reaction.
Thus, despite the processes described above, there remains a need in the art for a process for producing optically active cis-1,3-cyclohexanedicarboxylic acid monoesters that offers high enantioselectivity.